PubMed · 5864919
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P Zlatar. 1965. [Capsular pseudoexfoliation].. https://doi.org/10.1159/000304844
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PURPOSE: Traumatic cataract is a common blinding eye disease after ocular trauma, and its pathogenesis is closely related to lens epithelial cell dysfunction, while the definite molecular regulatory mechanism between upstream transcription factor and downstream target gene remains poorly clarified. This study aimed to clarify the role and molecular mechanism of the krüppel-like factor 5 (KLF5)/ thrombosponin 1 (THBS1) axis in regulating proliferation, migration, epithelial-mesenchymal transition and autophagy of lens epithelial cells in traumatic cataract, and to explore its potential clinical therapeutic value. METHODS: The GSE295383 dataset in the gene expression omnibus (GEO) database was downloaded, and the differentially expressed genes (DEGs) were screened by linear models for microarray data (limma) package of R language. Combined with Weighted gene co-expression network analysis (WGCNA), the gene co-expression network was constructed and the key modules were screened. Gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA) combined with human transcription factor target (hTFtarget) and JASPAR databases were used to predict the upstream transcription factors of THBS1. Subsequently, SRA01/04 cells were induced with transforming growth factor-beta 2 (TGF-β2) to construct a cataract cell model. RESULTS: THBS1 and KLF5 were highly expressed in LECs exposed to TGF-β2. KLF5 could activate THBS1 transcription by binding to THBS1 promoter - 174 to -165 sites. Knockdown of THBS1 inhibited TGF-β2-induced viability, proliferation, migration, and altered the expression of epithelial-mesenchymal transition (EMT)- and autophagy-related markers in LECs. Knockdown of KLF5 downregulated THBS1 expression and produced a similar inhibitory effect, while overexpression of THBS1 reversed the effect of KLF5 knockdown. CONCLUSIONS: This study demonstrated that KLF5 promoted the proliferation, migration, and EMT‑associated molecular changes of LECs in traumatic cataract through transcriptional activation of THBS1, and regulated the expression of autophagy‑related markers in LECs, suggesting that KLF5/THBS1 axis might be a potential target for the treatment of traumatic cataract.
PURPOSE: To identify ultrastructure changes and genetic defects associated with a special fasciculiform autosomal dominant congenital cataract (ADCC) affecting a large Chinese family. METHODS: Members of the Chinese family affected by this special fasciculiform ADCC were studied. Clinical examinations, light and transmission electron microscopy of the removed lens tissue, linkage analyses using polymorphisms of microsatellite markers, and mutational analyses of candidate genes by direct sequencing were performed. RESULTS: The thirteen affected individuals in the family showed no variability between one another. The lens fiber cells showed focal degeneration, dense globular intracellular deposits, and an enlarged intercellular space. This ADCC was associated with a locus on chromosome 2q33-35 (maximum lod score [Zmax]=3.34; theta=0.05). Mutational analyses of the candidate genes (gamma-crystallin; CRYG), identified a C->A heterozygous transversion at nucleotide position 70 in the gammaD-crystallin gene (CRYGD) exon2, which co-segregated with the presence of ADCCs and was not observed in 100 unrelated controls. CONCLUSIONS: This study identified ultrastructure changes and genetic defects associated with a special fasciculiform ADCC affecting a large Chinese family. It appeared to be caused by a missense mutation in the CRYGD gene, further supporting the notion that alterations to CRYG play an important factor in human cataract formation.
PURPOSE: Hereditary cataract is a clinically and genetically heterogeneous lens disorder that usually presents as a sight-threatening trait in childhood. The purpose of this study was to map and identify the mutation underlying an autosomal dominant form of coral-shaped cataract segregating in a three generation Caucasian pedigree. METHODS: Genomic DNA was prepared from blood leucocytes, genotyping was performed using microsatellite markers, and LOD scores were calculated using the LINKAGE programs. Mutation detection was performed using direct sequencing and primer extension analysis. Following site-directed mutagenesis, mutant and wild type expression constructs were transfected into a human lens epithelial cell line (HLE B-3) and recombinant protein was detected by immunoblotting, imunofluorescence, and immunogold microscopy. Cell death was monitored by fluorescence activated cell sorting. RESULTS: Significant evidence of linkage was detected at markers D2S371 (LOD score [Z]=3.81, recombination fraction [theta]=0) and D2S369 (Z=3.64, theta=0). Haplotyping indicated that the disease gene lay in the approximate 10 Mb physical interval between D2S1384 and D2S128, containing the gamma-crystallin gene (CRYGA-CRYGD) cluster on chromosome 2q33.3-q34. Sequencing of the CRYGA-CRYGD cluster identified a C->A transversion in exon 2 of CRYGD that was predicted to result in the non-conservative substitution of threonine for proline at amino-acid residue 23 (P23T) in the processed CRYGD protein. Transfection studies suggested that the P23T mutant was less soluble than its wild type counterpart when expressed in HLE B-3 cells. CONCLUSIONS: This study has identified an eighth type of cataract morphology associated with CRYGD and suggests that a CRYGD mutation may underlie the historically important "coralliform" cataract first reported in 1895.